TY - JOUR
T1 - Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101)
T2 - First-in-Human Clinical Trial in Patients with Advanced Metastatic Cancer
AU - Tsimberidou, Apostolia M.
AU - Guenther, Kerstin
AU - Andersson, Borje S.
AU - Mendrzyk, Regina
AU - Alpert, Amir
AU - Wagner, Claudia
AU - Nowak, Anna
AU - Aslan, Katrin
AU - Satelli, Arun
AU - Richter, Fabian
AU - Kuttruff-Coqui, Sabrina
AU - Schoor, Oliver
AU - Fritsche, Jens
AU - Coughlin, Zoe
AU - Mohamed, Ali S.
AU - Sieger, Kerry
AU - Norris, Becky
AU - Ort, Rita
AU - Beck, Jennifer
AU - Vo, Henry Hiep
AU - Hoffgaard, Franziska
AU - Ruh, Manuel
AU - Backert, Linus
AU - Wistuba, Ignacio I.
AU - Fuhrmann, David
AU - Ibrahim, Nuhad K.
AU - Morris, Van Karlyle
AU - Kee, Bryan K.
AU - Halperin, Daniel M.
AU - Nogueras-Gonzalez, Graciela M.
AU - Kebriaei, Partow
AU - Shpall, Elizabeth J.
AU - Vining, David
AU - Hwu, Patrick
AU - Singh, Harpreet
AU - Reinhardt, Carsten
AU - Britten, Cedrik M.
AU - Hilf, Norbert
AU - Weinschenk, Toni
AU - Maurer, Dominik
AU - Walter, Steffen
N1 - Publisher Copyright:
2023 American Association for Cancer Research.
PY - 2023/7/1
Y1 - 2023/7/1
N2 - IMA101 is an actively personalized, multi-targeted adoptive cell therapy (ACT), whereby autologous T cells are directed against multiple novel defined peptide-HLA (pHLA) cancer targets. HLA-A02:01-positive patients with relapsed/refractory solid tumors expressing ≥1 of 8 predefined targets underwent leukapheresis. Endogenous T cells specific for up to 4 targets were primed and expanded in vitro. Patients received lymphodepletion (fludarabine, cyclophosphamide), followed by T-cell infusion and low-dose IL2 (Cohort 1). Patients in Cohort 2 received atezolizumab for up to 1 year (NCT02876510). Overall, 214 patients were screened, 15 received lymphodepletion (13 women, 2 men; median age, 44 years), and 14 were treated with T-cell products. IMA101 treatment was feasible and well tolerated. The most common adverse events were cytokine release syndrome (Grade 1, n ¼ 6; Grade 2, n ¼ 4) and expected cytopenias. No patient died during the first 100 days after T-cell therapy. No neurotoxicity was observed. No objective responses were noted. Prolonged disease stabilization was noted in three patients lasting for 13.7, 12.9, and 7.3 months. High frequencies of target-specific T cells (up to 78.7% of CD8þ cells) were detected in the blood of treated patients, persisted for >1 year, and were detectable in posttreatment tumor tissue. Individual T-cell receptors (TCR) contained in T-cell products exhibited broad variation in TCR avidity, with the majority being low avidity. High-avidity TCRs were identified in some patients’ products. This study demonstrates the feasibility and tolerability of an actively personalized ACT directed to multiple defined pHLA cancer targets. Results warrant further evaluation of multi-target ACT approaches using potent high-avidity TCRs.
AB - IMA101 is an actively personalized, multi-targeted adoptive cell therapy (ACT), whereby autologous T cells are directed against multiple novel defined peptide-HLA (pHLA) cancer targets. HLA-A02:01-positive patients with relapsed/refractory solid tumors expressing ≥1 of 8 predefined targets underwent leukapheresis. Endogenous T cells specific for up to 4 targets were primed and expanded in vitro. Patients received lymphodepletion (fludarabine, cyclophosphamide), followed by T-cell infusion and low-dose IL2 (Cohort 1). Patients in Cohort 2 received atezolizumab for up to 1 year (NCT02876510). Overall, 214 patients were screened, 15 received lymphodepletion (13 women, 2 men; median age, 44 years), and 14 were treated with T-cell products. IMA101 treatment was feasible and well tolerated. The most common adverse events were cytokine release syndrome (Grade 1, n ¼ 6; Grade 2, n ¼ 4) and expected cytopenias. No patient died during the first 100 days after T-cell therapy. No neurotoxicity was observed. No objective responses were noted. Prolonged disease stabilization was noted in three patients lasting for 13.7, 12.9, and 7.3 months. High frequencies of target-specific T cells (up to 78.7% of CD8þ cells) were detected in the blood of treated patients, persisted for >1 year, and were detectable in posttreatment tumor tissue. Individual T-cell receptors (TCR) contained in T-cell products exhibited broad variation in TCR avidity, with the majority being low avidity. High-avidity TCRs were identified in some patients’ products. This study demonstrates the feasibility and tolerability of an actively personalized ACT directed to multiple defined pHLA cancer targets. Results warrant further evaluation of multi-target ACT approaches using potent high-avidity TCRs.
UR - http://www.scopus.com/inward/record.url?scp=85164240250&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85164240250&partnerID=8YFLogxK
U2 - 10.1158/2326-6066.CIR-22-0444
DO - 10.1158/2326-6066.CIR-22-0444
M3 - Article
C2 - 37172100
AN - SCOPUS:85164240250
SN - 2326-6066
VL - 11
SP - 925
EP - 945
JO - Cancer Immunology Research
JF - Cancer Immunology Research
IS - 7
ER -